View source for 8e2e


==Cryo-EM structure of helical arch of BIRC6 (from local refinement 1)==
<StructureSection load='8e2e' size='340' side='right'caption='[[8e2e]], [[Resolution|resolution]] 1.98&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8e2e]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8E2E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8E2E FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 1.98&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8e2e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8e2e OCA], [https://pdbe.org/8e2e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8e2e RCSB], [https://www.ebi.ac.uk/pdbsum/8e2e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8e2e ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BIRC6_HUMAN BIRC6_HUMAN] Anti-apoptotic protein which can regulate cell death by controlling caspases and by acting as an E3 ubiquitin-protein ligase. Has an unusual ubiquitin conjugation system in that it could combine in a single polypeptide, ubiquitin conjugating (E2) with ubiquitin ligase (E3) activity, forming a chimeric E2/E3 ubiquitin ligase. Its tragets include CASP9 and DIABLO/SMAC. Acts as an inhibitor of CASP3, CASP7 and CASP9. Important regulator for the final stages of cytokinesis. Crucial for normal vesicle targeting to the site of abscission, but also for the integrity of the midbody and the midbody ring, and its striking ubiquitin modification.<ref>PMID:14765125</ref> <ref>PMID:15200957</ref> <ref>PMID:18329369</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Tight regulation of apoptosis is essential for metazoan development and prevents diseases such as cancer and neurodegeneration. Caspase activation is central to apoptosis, and inhibitor of apoptosis proteins (IAPs) are the principal actors that restrain caspase activity and are therefore attractive therapeutic targets. IAPs, in turn, are regulated by mitochondria-derived proapoptotic factors such as SMAC and HTRA2. Through a series of cryo-electron microscopy structures of full-length human baculoviral IAP repeat-containing protein 6 (BIRC6) bound to SMAC, caspases, and HTRA2, we provide a molecular understanding for BIRC6-mediated caspase inhibition and its release by SMAC. The architecture of BIRC6, together with near-irreversible binding of SMAC, elucidates how the IAP inhibitor SMAC can effectively control a processive ubiquitin ligase to respond to apoptotic stimuli.

Structures of BIRC6-client complexes provide a mechanism of SMAC-mediated release of caspases.,Hunkeler M, Jin CY, Fischer ES Science. 2023 Mar 17;379(6637):1105-1111. doi: 10.1126/science.ade5750. Epub 2023 , Feb 9. PMID:36758104<ref>PMID:36758104</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8e2e" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Fischer ES]]
[[Category: Hunkeler M]]